Wound Repair and Regeneration最新文献

Photobiomodulation (PBM) therapy is a continuously growing approach to stimulating healing and reducing inflammation and pain. However, its effects in the fields of regenerative medicine and tissue engineering are still under investigation. Studying PBM effects on the regenerative capacity of zebrafish can allow the application of novel clinical approaches where the impact of PBM will be cross-linked with the stem-cell therapeutic approaches. This study was done to establish an in-vivo experimental setup for studying the effects of laser and ultraviolet therapy on zebrafish caudal-fin regeneration and vascularization. Thirty zebrafish were randomly and equally allocated into three groups. The caudal-fins of all zebrafish were amputated under anaesthesia. In the first control group, the caudal-fin was only monitored until fully regenerated. In the second group, the amputated-fin was irradiated with ultraviolet. Finally, in the third group, the amputated-fin was irradiated with laser. Caudal-fin regeneration and vascularization were assessed at days 0, 3, 6, 9, 12, and 15 in all fish. In terms of regeneration, the results indicated that it is possible to discriminate the regenerative effect of laser with the experimental setup as laser therapy showed a statistically significant difference when compared to control-group. It was also found that regenerative stimulation of the group that received ultraviolet therapy showed significant difference when compared to the control group. In terms of vascularization, there was a statistically significant difference in all groups of the study, which may suggest that laser as well as ultraviolet have limited effects in terms of improving vascularization. This study presented a novel, simple and inexpensive method for the assessment of PBM effects on zebrafish. Laser and ultraviolet therapy appeared to act as regenerative stimulators for caudal-fin regeneration of zebrafish. However, laser therapy results were, to some extent, better than ultraviolet therapy. This novel in-vivo design of the experiment led to more rapid and reproducible results than in-vitro experiments.

Traditional wound dressings, despite their widespread use, face limitations, such as poor infection control and insufficient healing promotion. To address these challenges, bioactive materials have emerged as a promising solution in wound care. This comprehensive review explores the latest developments in wound healing technologies, starting with an overview of the importance of effective wound management, emphasising the need for advanced bioactive wound dressings. The review further explores various bioactive materials, defining their characteristics. It covers a wide range of natural and synthetic biopolymers used to develop bioactive wound dressings. Next, the paper discusses the incorporation of bioactive agents into wound dressings, including antimicrobial and anti-inflammatory agents, alongside regenerative components like growth factors, platelet-rich plasma, platelet-rich fibrin and stem cells. The review also covers fabrication techniques for bioactive wound dressings, highlighting techniques like electrospinning, which facilitated the production of nanofibre-based dressings with controlled porosity, the sol-gel method for developing bioactive glass-based dressings, and 3D bioprinting for customised, patient-specific dressings. The review concludes by addressing the challenges and future perspectives in bioactive wound dressing development. It includes regulatory considerations, clinical efficacy, patient care protocol integration and wound healing progress monitoring. Furthermore, the review considers emerging trends such as smart materials, sensors and personalised medicine approaches, offering insights into the future direction of bioactive wound dressing research.

The stromal vascular fraction of adipose tissue has gained popularity as regenerative therapy for tissue repair. Both enzymatic and mechanical intraoperative SVF isolation procedures exist. To date, the quest for the preferred isolation procedure persists, due to the absence of standardised yield measurements and a defined clinical threshold. This systematic review is an update of the systematic review published in 2018, where guidelines were proposed to improve and standardise SVF isolation procedures. An elaborate data search in MEDLINE (PubMed), EMBASE (Ovid) and the Cochrane Central Register of Controlled Trials was conducted from September 2016 to date. A total of 26 full-text articles met inclusion criteria, evaluating 33 isolation procedures (11 enzymatic and 22 mechanical). In general, enzymatic and mechanical SVF isolation procedures yield comparable outcomes concerning cell yield (2.3-18.0 × 10⁵ resp. 0.03-26.7 × 10⁵ cells/ml), and cell viability (70%-99% resp. 46%-97.5%), while mechanical procedures are more time consuming (8-20 min vs. 50-210 min) and cost-efficient. However, as most studies used poorly validated outcome measures on SVF characterisation, it still remains unclear which intraoperative SVF isolation method is preferred. Future studies are recommended to implement standardised guidelines to standardise methods and improve comparability between studies.

To gain a clearer understanding of the relationship between venous leg ulcers (VLUs) and knee osteoarthritis (KOA), we performed a two-sample, bidirectional Mendelian randomization (MR) analysis in this study. The present MR was carried out using summary data from publicly available genome-wide association studies. After filtering single-nucleotide polymorphism (SNP), we applied a variety of MR methods including inverse variance weighted (IVW), MR egger, weighted mode, and weighted median. IVW analysis revealed that the genetic association between VLUs and KOA was not significant (β = -0.017; SE 0.039; p = 0.658). In agreement with the IVW analysis, the findings of the weighted median estimator (β = -0.017; SE 0.052, p = 0.751), MR egger (β = 0.057; SE 0.084; p = 0.513), and weighted mode (β = 0.060; SE 0.078; p = 0.456) indicated the absence of a significant genetic association between VLUs and KOA. Furthermore, reverse causality analysis suggested a lack of genetic relationship between KOA and VLUs. In conclusion, the present MR study does not suggest a causal relationship or reverse causal relationship between VLUs and KOA.

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm-forming bacteria. As one of the most abundant skin-commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm-forming capability and pro-inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re-epithelialization through biofilm-dependent induction of IL-1β, IL-8, and IL-6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment-resistant virulent lineages in patients with chronic ulcers.

Dermal substitutes have been introduced in burn care to improve wound healing outcomes; however, their use remains limited in standard treatments. This systematic review and meta-analysis aimed to evaluate the outcomes of dermal substitutes in patients with burns and patients requiring burn scar reconstruction and subsequently contribute to optimising the integration of dermal substitutes into clinical practice and reducing the knowledge gap. A comprehensive search across various databases included human studies from peer-reviewed journals on dermal substitutes for deep dermal and full-thickness burns, and scar reconstruction across all ages. Data from comparative trials were extracted, focusing on patient and wound characteristics, treatment specifics, and outcomes related to wound healing and scar quality. Meta-analysis was performed on trials reporting similar post-burn measures, with statistical heterogeneity assessed. Outcomes were presented using mean differences or odds ratios with 95% confidence intervals. A total of 31 comparative trials were included. The overall quality of the studies was considered moderate. The meta-analysis indicated delayed re-epithelialization 4-7 days after treatment with a collagen-elastin matrix compared to split-thickness skin graft in acute burns (-7.30%, p = 0.02). Significant improvement in subjective scar quality was observed with acellular dermal matrix compared to split-thickness skin graft in acute burn wounds 6 months post-operative (-1.95, p <0.01). While acknowledging the initially delayed wound healing, incorporating dermal substitutes into the surgical treatment of burn patients holds promise for enhancing scar quality. However, future research must prioritise outcome measure uniformity, address variations in dermal substitute application, and standardise indications for consistent and effective practices.

The presence of microbial biofilms in many human chronic wounds led to the hypothesis that biofilms delay healing of these wounds. We tested this hypothesis in a population of 117 older individuals with venous leg ulcers who were receiving standardised therapy, including frequent debridement. Debridement specimens were analysed for the amount of bacterial biomass by two independent methods: a microscopic approach that scored the relative size and number of bacterial aggregates, interpreted as a biofilm metric, and conventional enumeration by agar plating for viable bacteria. The plating protocol yielded three distinct values: the total viable bacterial count, bleach-tolerant bacteria, and the log reduction in viable bacteria upon bleach treatment. Wound healing rates over an 8-week observation period were calculated as the rate of decrease of the equivalent diameter of the wound. There was no statistically significant association between wound healing and the biofilm metric in any of the three analyses performed (p ≥0.15). In all three statistical tests, wound healing was associated with the log reduction caused by bleach treatment (p ≤0.004); wounds that harboured bacteria that were more bleach-susceptible healed more slowly. A refinement of the model of chronic wound infection pathogenesis is proposed in which dormant bacteria constitute a persistent nidus and outgrowth of metabolically active cells impairs healing. This model constitutes a new hypothesis as metabolic activity was not directly measured in this investigation.

The aim of this meta-analysis is to compare the clinical outcomes in patients with and without residual osteomyelitis (ROM) after surgical bone resection for diabetic foot osteomyelitis (DFO). We completed a systematic literature search using PubMed, Scopus, and Embase using keywords DFO, Residual OM (ROM), and positive bone margins. The study outcomes included wound healing, antibiotic duration, amputation, and re-infection. Five hundred and thirty patients were included in the analysis; 319 had no residual osteomyelitis (NROM), and 211 had ROM. There was not a significant difference in the proportion of wounds that healed 0.6 (p = 0.1, 95% confidence intervals [95% CI] 0.3-1.3). The risk of infection was 2.0 times higher (OR = 2.0, p = 0.02, 95% CI 1.1-3.4), and the risk of amputation was 4.3 times higher (OR = 4.3, p = 0.0001, 95% CI 2.4-7.6) in patients with ROM. Patients with ROM received antibiotics significantly longer. The mean difference was 16.3 days (p = 0.02, 95% CI 11.1-21.1).

Bioengineered allogeneic cellularised constructs (BACC) exert pro-healing effects in burn wounds and skew macrophage phenotype towards a predominately reparative phenotype. However, whether BACC can modulate the phenotype of dysregulated macrophages, like those present in burn wounds, is not known. To better understand the macrophage modulatory characteristics of the BACC, primary human macrophages were polarised to the M2b phenotype, an immunosuppressive phenotype relevant to burn wounds, by simultaneously exposing macrophages to polystyrene plate-coated immunoglobulin G and the endotoxin lipopolysaccharide (LPS). The resulting macrophage phenotype upregulated both inflammatory and reparative genes, and increased secretion of the M2b marker CCL1 compared to five different in vitro macrophage phenotypes. M2b macrophages were cultured with the BACC in the presence or absence of LPS to mimic infection, which is a common occurrence in burn wounds. The BACC caused up-regulation of reparative gene sets and down-regulation of pro-inflammatory gene sets, even when LPS was present in the cell culture media. Co-cultures were maintained for 1, 3, or 5 days in the presence of LPS, and by day 1 both non-activated macrophages and M2b macrophages exhibited signs of endotoxin tolerance, as demonstrated by a reduced secretion of tumour necrosis factor α (TNFα) in response to fresh LPS stimulus. The BACC was not able to prevent endotoxin tolerance, but reparative genes were upregulated in macrophages chronically exposed to LPS. These results suggest that the BACC can promote a reparative phenotype in dysregulated macrophages relevant to the pathophysiology of burns.

Scleroderma or systemic sclerosis (SSc)-associated digital ischaemic complications, such as digital ulcers (SSc-DUs), appear relatively early during the disease course and are a major burden with substantial deterioration of quality of life. Expert rheumatologist and wound specialists have defined a DU; however, international application of the definition is still disorganised. Appearance of SSc-DUs is secondary to the onset of Raynaud's phenomenon and as a consequence, recommended first-line of treatment mainly includes vasodilators; however, many DUs are refractory to this treatment. Despite important practical issues, such as a lack of well-characterised SSc-wound healing animal model, significant efforts are needed to mechanistically understand the pathogenesis of SSc-DUs for developing clinically targetable disease modifying therapies.